In pharmaceutical technology, there are two known principal systems which effect distribution or dissolution of compressed forms in water, these being the disintegrating tablet on the one hand and the effervescent tablet on the other hand.
In the case of the disintegrating tablet, disintegrants which are added to the tablets cause it to disintegrate after some time in water or in gastric fluid and to release the active substances.
The disintegrating tablets have the disadvantage that their disintegration occurs locally, i.e. they disintegrate at the bottom of the class, and the disintegrated particles remain there, or, owing to the disintegration system, they can give rise to local concentrations in the stomach itself. Disintegrating tablets are therefore not expedient for various active substances.
In addition, disintegrating tablets are difficult to formulate, particularly in the presence of water-soluble substances, since it is known that, after the beginning of disintegration of the tablet, a core remains which does not continue disintegrating or disintegrates to an insufficient extent. Another aspect is acceptance of the flavor of the disintegrating tablet, since certain disintegrants can give rise to an unpleasant flavor.
Another system comprises effervescent tablets in which a reaction between organic acids and bicarbonates or carbonates causes dissolution, carbon dioxide being eliminated from bicarbonates or carbonates; during this process, active substances are distributed or dissolved in a glass of water.
However, the effervescent tablet has the disadvantage that it has to be relatively large and heavy compared with the disintegrating tablet, since the amount of effervescent mixture present must be significantly larger than that of active substance in order to distribute or dissolve the latter or to achieve an appropriate rate.
Attempts have already been made to prepare an effervescent tablet which both disintegrates and effervesces. Such a tablet, which consists of two layers, namely an effervescent layer and a disintegrating tablet, has been disclosed by U.S. Pat. No. 4,832,956. However, this system has the disadvantages that it still requires a large amount of effervescent constituents and nevertheless fails to provide particularly rapid distribution because the effervescent layer becomes lighter owing to the gas formation in the water and the tablet therefore turns so that the effervescent layer faces upward and dissolves more rapidly than the lower disintegrating tablet layer, the disintegrating particles then falling to the bottom of the glass. Furthermore, a two-layer tablet press is required for this purpose, which in turn means greater technical complexity and is therefore uneconomical from the point of view of production technology.
It was previously believed that the components of the two systems would interfere with one another.
Disintegrants in a tablet, for example, starch, microcellulose or crosslinked polyvinylpolypyrrolidone, function all the poorer the more water-soluble the accompanying substances of the tablet. This is due to the fact that the water solubility of the accompanying substances or active substances causes the capillaries of the tablet and of the disintegrant to be blocked, and the resulting concentrated solutions prevent disintegration.
Thus, if an effervescent tablet containing relatively large amounts of disintegrants is prepared, the disintegrant does not function nor does the tablet effervesce, and compressed forms which take several minutes to dissolve are formed.
This also applies to pharmaceutical formulations according to Brit. Pat. 1093286 or U.S. Pat. No. 4289751.
In the Brit. Pat., mixtures of an effervescent system with a disintegrant are filled into a gelatine capsule which is resistant to gastric fluid, swells in the duodenum and bursts owing to the internal evolution of gas. Such a capsule exhibits virtually no solubility in water; if the mixture, for example from Example 2 stated there, is pressed to give an uncoated tablet, only isolated gas bubbles are evolved when the tablet is introduced into water; the tablet dissolves very slowly and takes as long as 20 to 30 minutes.
The U.S. Patent, too, describes a coated tablet which is resistant to gastric fluid and is intended to release its active substance only in the intestine. The combination of an effervescent system with a disintegrant is intended here to achieve better distribution in the intestine; whether the time for disintegration or for dissolution or for the effervescent effect in the intestine is 30 seconds or 30 minutes plays absolutely no role here. In fact, the tablets described there require 120 seconds or more for dissolution, even without a coating. This is certainly partly due to the microcrystalline cellulose which, according to claim 9, is also used there as a dry binder and which, for the purposes of the present invention described below, is not to be regarded as a disintegrant, as will be shown further below in Example 17.
It is the object of the invention to develop a tablet which combines the essential advantages of both the disintegrating tablet and the effervescent tablet in one system.